The overall goal of the Genetics and Genomics (GG) Program is to discover novel cancer genes, to elucidate the function of diverse genetic and epigenetic states, to translate mechanistic insight into therapeutic targets and associated biomarkers, and to accelerate the delivery of precision cancer medicine to our patients. This will be accomplished in three aims: Aim 1 ? To interrogate genetic drivers of tumor hallmarks; Aim 2 ? To delineate epigenetic states as biomarkers and targets in cancer, and Aim 3 ? To translate of genetic and epigenetic discovery toward clinical application. A number of important scientific discoveries emanated from the GG Program that illustrate the overall research depth, cancer focus, and added value. Additionally, the GG Program developed unique tumor sequencing data and analysis approaches to support precision medicine concepts. For example, panels developed within the GG Program were leveraged toward the development of a molecular diagnostic company (OmniSeq) that contributes to the recruitment of Roswell Park patients into molecular basket trials, such as NCI-MATCH. The GG Program research portfolio encompasses studies addressing genetic basis of aggressiveness of hormone refractory breast and prostate cancer in African- American populations ? cancers that are of particular importance for our WNY catchment area. John Krolewski, MD, PhD and Erik Knudsen, PhD are new co-Leaders for the Program who have strong interests in basic, clinical, and population aspects of tumor genetics and epigenetics. Dr. Krolewski's leadership efforts focus on signaling/cytokine pathways and genomics of genitourinary malignancies, which complements Dr. Knudsen's focus in the areas of cell cycle control and genomic stability, and targeting such pathways in breast and gastrointestinal cancers. The Program is comprised of 27 members from nine Roswell Park departments/centers (Cancer Genetics and Genomics, Center for Personalized Medicine, Molecular and Cellular Biology, Pharmacology and Therapeutics, Urology, Thoracic Surgery, Biostatistics and Bioinformatics, Medicine, and Pathology), whose total peer-reviewed funding is $3.1M direct costs (NCI funding $1.9M direct) and a total funding of $5.4M direct costs. Since the last renewal, 12 new members (nine recruited from outside Roswell Park) have joined the Program. Of the 385 publications generated over the last funding cycle, 9% are intra-programmatic and 44% are inter-programmatic; 50 (13%) publications are in journals with an impact factor >10. Future goals of the Program are focused on multi-investigator projects that make impactful discoveries and translate basic science into the clinical arena, harnessing GG science to target cancers at the genetic and epigenetic levels.